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20q– Clonality in a Case of Oral Sweet Syndrome and Myelodysplasia

Katherine Van Loon MD, MPH, Ryan M. Gill MD, PhD, Patrick McMahon MD, Radhika Chigurupati DMD, Imran Siddiqi MD, Lindy Fox MD, Lloyd Damon MD, Timothy H. McCalmont MD, Richard Jordan DDS, PhD, Jeffrey Wolf MD
DOI: http://dx.doi.org/10.1309/AJCP9I7NRWYLTJHV 310-315 First published online: 1 February 2012


We report the case of a patient with myelodysplasia who had Sweet syndrome of the oral cavity. An atypical myeloid immunophenotype was present in the gingival biopsy specimen and in a concurrent bone marrow specimen. Fluorescence in situ hybridization performed on the gingival biopsy specimen demonstrated the same del(20q) cytogenetic abnormality present in the bone marrow, confirming the presence of a clonally related myeloid proliferation in both tissues. This is the first reported case of Sweet syndrome and myelodysplasia in which the chromosomal abnormality was identified in the neutrophilic infiltrate, confirming the neutrophilic infiltrate to be clonally related to the underlying myeloid neoplasm.

Key Words
  • Sweet syndrome
  • Myelodysplasia
  • Acute myelogenous leukemia
  • Neutrophilic dermatosis
  • Clonality

Sweet syndrome was originally described by Dr Robert Douglas Sweet in 1964 as an “acute febrile neutrophilic dermatosis.”1 It is a rare condition characterized by pyrexia, leukocytosis, painful erythematous papules and plaques, and a rapid response to systemic corticosteroids. Microscopically, there is a dense, interstitial, neutrophilic infiltrate in the biopsy specimens of lesional tissues. While the cause of the syndrome remains unknown, approximately 20% of cases occur in conjunction with an underlying malignancy, the majority of which are hematologic in origin.2 Of the hematologic conditions with which it is associated, the most prevalent are myelodysplastic syndrome and acute myelogenous leukemia (AML).

Case Report

Our patient was a 38-year-old man who had been given a diagnosis of AML with a normal karyotype and myelomonocytic differentiation 34 months earlier. He underwent induction chemotherapy with cytarabine and daunorubicin and 3 cycles of consolidation with high-dose cytarabine. He experienced relapse after 1 year and was referred to our institution, where he underwent reinduction with idarubicin, etoposide, and cytarabine. A bone marrow biopsy following reinduction therapy demonstrated persistent AML, with 6% blasts and the following new cytogenetic abnormalities: inv(9),del(20) (q11.2). He was treated with gemtuzumab ozogamicin, fludarabine, and cytarabine; however, a repeated bone marrow biopsy demonstrated 6% blasts and del(20)(q11.2) in 12 of 17 mitotic cells, consistent with residual AML. Five months before the hospitalization described subsequently, a bone marrow biopsy demonstrated a hypocellular marrow with 4% to 5% myeloid blasts and the same cytogenetic abnormality. The bone marrow findings were interpreted as consistent with myelodysplasia, and therapy was initiated with monthly 5-azacitadine.

Hospitalization Course

On the day of admission, the patient was tachycardic and febrile (temperature to 40.6°C). Inspection of the palate revealed 2 small, painful hemorrhagic lesions. Laboratory data demonstrated a WBC count of 7,200/μL (7.2 × 109/L), hemoglobin concentration of 10.3 g/dL (103 g/L), and platelet count of 8,000/μL (8 × 109/L). Magnetic resonance imaging demonstrated abnormal T2 hyperintensity and contrast enhancement in the right malar soft tissues and the right buccal space and mucosal thickening of the right maxillary sinus, without evidence of an organized fluid collection Image 1A. On hospital day 4, intraoral examination revealed rapid progression of an infiltrative papillated plaque throughout almost the entire palate Image 1B. The patient underwent debridement and biopsy of the mucosal lesions and maxillary sinus lining, with intraoperative examination revealing friable oral mucosa with patches of necrotic tissue and newly mobile teeth. A Gram stain was negative; however, tissue culture grew Enterococcus faecalis. Fungal cultures, herpes simplex virus culture, Histoplasma antigen testing, and cryptococcal antigen testing were all negative.

During the next 2 weeks, the palatal lesions gradually reepithelialized; however, the patient continued to have high-spiking fevers despite broad-spectrum microbial coverage. A bone marrow biopsy demonstrated a blast population of less than 5% of nucleated cells and no evidence for AML recurrence; the previously detected del(20q) was present in 29 of 30 cells examined. On hospital day 19, the palatal lesion progressed rapidly. Fiberoptic endoscopy demonstrated a verrucous, erythematous, ulcerative lesion across the entire palate, extending posteriorly to involve the soft palate and uvula to its inferior aspect. On hospital day 24, a deep maxillary sinus lining biopsy was performed with pathologic demonstration of a diffuse neutrophilic infiltrate with leukocytoclasis, consistent with Sweet syndrome. High-dose corticosteroid therapy was started, which resulted in immediate regression of the oral lesions.

Pathologic Diagnosis

Microscopic examination of the gingival tissue sections demonstrated a dense, sheet-like infiltrate of mature neutrophils mixed with hemorrhage Image 2A and focal necrosis and thrombosis Image 2B. Cells were variably sized with segmented nuclei and occasionally increased nuclear/cytoplasmic ratios Image 2C but without a discernible immature population by morphologic or immunohistochemical studies (myeloperoxidase-positive, Image 2D; CD34–, Image 2E). Flow cytometric evaluation of gingival tissue demonstrated a predominant population of mature myeloid cells with variable side scatter, expressing intermediate CD45, CD11c, and CD13; weak CD14, CD15, CD64, and myeloperoxidase; weak HLA-DR; weak to absent CD33; and absent CD34, CD61, CD117, terminal deoxynucleotidyl transferase, and other lymphoid antigens. While the expression of CD14 and CD64 and relative lack of CD33 are atypical findings in mature neutrophils, they are not independently diagnostic of a myeloid malignancy because up-regulation of CD14 and CD64 can be seen during neutrophil transdifferentiation in active inflammatory processes. However, a similar atypical myeloid immunophenotype was present in the concurrent bone marrow specimen, and, it is important to note, fluorescence in situ hybridization (FISH) performed on the gingival biopsy specimen demonstrated the presence of the same del(20q) in the neutrophilic infiltrate Image 2F, confirming the presence of a clonally related myeloid proliferation in the gingival tissue and bone marrow.

Image 1

A, Magnetic resonance imaging of the face demonstrated abnormal T2 hyperintensity, contrast enhancement in the malar soft tissues and in the right buccal space, and new mucosal thickening of the right maxillary sinus without evidence of an organized fluid collection. B, On hospital day 4, intraoral examination revealed an infiltrative hemorrhagic plaque over the hard palate extending from the right to the left side across the midline and anteroposteriorly from the right central incisor to the second molar region.

Image 2

Gingival biopsy. A, Sheet-like infiltrate of neutrophils involving mucosa and lamina propria with associated hemorrhage (H&E, ×100). B, Focal areas of necrosis and thrombosis with associated neutrophilic infiltrate (H&E, ×200). C, Neutrophils demonstrating variable segmentation and increased nuclear/cytoplasmic ratios (H&E, ×400). D, Immunohistochemical analysis for myeloperoxidase shows expression in neutrophils (×200). E, Negative immunohistochemical expression of CD34 in neutrophils (×200). F, Arrows indicate 20q deletion, shown by fluorescence in situ hybridization, D20S108 probe (red), 20qter probe (green) (×1,000; contributed by Rhett Ketterling, MD, Mayo Clinical Laboratories, Rochester, MN).


Our differential diagnosis for this case included infections such as mucormycosis, histoplasmosis, actinomycosis, nocardiosis, herpes simplex virus mucositis, and tuberculosis. Evolution of the patient’s underlying myelodysplasia to leukemia cutis/myeloid sarcoma was also considered. Finally, reactive or inflammatory conditions were considered, including pyoderma gangrenosum, pseudolymphoma, sarcoidosis, and Sweet syndrome.

While Sweet syndrome most commonly manifests with a febrile illness associated with painful, edematous, erythematous papules, nodules, and plaques on the skin, myriad extracutaneous manifestations, including neutrophilic infiltration of eyes, ears, heart, lungs, central nervous system, intestines, kidneys, joints, and oral mucosa have been described. Although idiopathic oral Sweet syndrome has been reported,36 it is more commonly seen in association with an underlying hematologic malignancy.7 In addition, our patient had recently received treatments with granulocyte colony-stimulating factor (G-CSF) and a hypomethylating agent, both of which have been reported in association with Sweet syndrome.8,9 A review of the published cases of Sweet syndrome involving the oral mucosa indicates that this condition may present with a broad spectrum of clinical manifestations, which often mimic other conditions Table 1.36,8,1015

There have been several reports on the association of Sweet syndrome with myelodysplasia; however, the pathogenesis of the neutrophilic dermatosis remains poorly understood. Reports of the presence of the Pelger-Huët anomaly in a cutaneous infiltrate provided the first indication that cells of the underlying myeloid neoplasm might coexist with the typical inflammatory cells seen in Sweet syndrome.16,17 A case of Sweet syndrome that occurred in the setting of G-CSF administered for treatment of neutropenia following induction chemotherapy for AML generated a hypothesis that the syndrome involves maturation of immature myeloid cells into clonally restricted dysplastic neutrophils.18

View this table:
Table 1

By using X-inactivation assays, clonal restriction of neutrophils was found in biopsy specimens of the neutrophilic dermatoses in patients with and without an underlying myeloid neoplasm.19 In a patient with chronic myelogenous leukemia, FISH analysis revealed the BCR-ABL fusion gene, indicative of the presence of translocation t(9;22)(q34;q11) in a neutrophilic skin infiltrate that was consistent with Sweet syndrome, although the authors did not rule out an immature immunophenotype for the infiltrate; thus, it is uncertain if this case represents immature chronic myelogenous leukemia cells intermingled with neutrophils or if the neoplastic cells underwent maturation to a clonal neutrophilic infiltrate.20 Sweet syndrome has also been reported in association with all-trans retinoic acid administered for the treatment of acute promyelocytic leukemia, whereby all-trans retinoic acid–induced differentiation of neoplastic cells resulted in a clonal population of neutrophils present in skin lesions.21

In this case, the patient had a 20q deletion in all 20 metaphase cells analyzed in the bone marrow, without a corresponding increase in blasts. The presence of sterile neutrophilia and the patient’s clinical response to systemic corticosteroids are consistent with the diagnosis of Sweet syndrome. Moreover, the neutrophils in the tissue infiltrates had a similar atypical immunophenotype to that of the marrow cells by flow cytometry and demonstrated the same 20q deletion. To our knowledge, this is the first reported case of Sweet syndrome and myelodysplasia in which the chromosomal abnormality was identified in the neutrophilic infiltrate, thus confirming the neutrophilic infiltrate to be clonally related to the underlying myeloid neoplasm. It is important to recognize that clonal myeloid infiltrates in patients with underlying myeloid neoplasms are not necessarily representative of a myeloid sarcoma and should not be treated as such, as indicated by our patient’s clinical response to corticosteroids.


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